DESCRIPTION (Taken from the Applicant?s Abstract) The applicants propose to become members of the Comparative Mouse Genomics Centers Consortium. A diverse group of investigators from four different institutions will participate in this program. The Kolodner laboratory will identify novel genes involved in DNA repair and DNA replication and examine the human population for polymorphisms that have functional significance. The functional importance of the polymorphisms will be assessed by the Kolodner and Kunkel laboratories by using yeast-based assays. The Edelmann and Kucherlapati laboratories will use modern gene modification technologies to generate mice that have null and specific point mutations in genes of interest. The Kunkel laboratory will characterize the biochemical properties of cells obtained from the mutant mice, and the Wang laboratory will examine the effects of DNA damaging agents on these mice. The Russell and Lipkin laboratories will examine the pathological consequences of the mutations under normal and different dietary regimens. The participating laboratories have experience in molecular biology, cell biology, and pathology. In addition, this group will bring several new technologies for the Consortium. These include high throughput physical mapping of segments of the mouse genome, high throughput DNA sequencing, and genetic analysis methods. The Kucherlapati laboratory will also bring expertise in the use and analysis of DNA microarray technologies including cDNA and oligonucleotide array methods. They also propose to develop tissue arrays. Experience in bioinformatics will be used to disseminate the data generated by this group. The investigators also propose to develop and implement novel technologies that might be of value to all members of the consortium.